The Epidermal Growth Factor Receptor (EGFR) is one member of Epidermal Growth Factor Receptor gene (erbB) family, which is over-expressed in about 30% human tumours, especially in non-small cell lung cancer, head and neck squamous cell carcinoma and colorectal cancer, and the like. Many studies at home and abroad have demonstrated that the antibodies against the EGFR show better therapeutic effect to various human tumours caused by EGFR over-expression or/and mutation, especially head and neck squamous cell carcinoma (80%-100%), colorectal cancer (25%-77%), non-small cell lung cancer (40%-80%), and the like, by means of effectively blocking the binding of the ligands extracellularly to inhibit the EGFR signal transduction pathway. The Epidermal Growth Factor Receptor has become one of tumour treating targets that currently are deeply studied and attract much attention. Using gene engineering to research and prepare the anti-EGFR monoclonal antibody has become one of research hotspots in tumour immune treatment.
In 2004 and 2006, U.S. FDA successfully approved murine-human chimeric antibody cetuximab and whole human antibody panitumumab against EGFR for the treatment of colorectal cancer; and in 2005, anti-EGFR humanized antibody nimotuzumab obtained the first class of new drug certificate approved by the Chinese State Food and Drug Administration (SFDA), and currently, its II/III phase clinical trials are being performed. When used in human body, the murine derived monoclonal antibody may elicit human anti-murine antibody response, thereby to negatively impacting its function. Engineered murine-human chimeric antibody with gene engineering technique may greatly reduce immunogenicity of murine monoclonal antibody, prolong the half life period of antibody in the body, and mediate immune adjustment and ADCC effect with the help of human immunoglobulin Fc fragments, thereby to enhance the biological effect of the antibody. However, the ability to bind antigen of the chimeric antibody is 98.7% lower than that of murine derived antibody. It has been demonstrated by many pre-clinical trials and clinical trials that cetuximab alone and in combination with chemotherapy/radiotherapy show better therapeutic effect. However, a simple CDR graft tends to cause the decrease of binding affinity between an antigen and an antibody. The panitumumab is a fully human antibody prepared with transgenic mouse technologies, and as compared with chimeric antibody and humanized antibody, has almost 100% humanized sequence, which greatly enhances binding affinity between the antibody and a target. However, such antibody shows drawbacks such as murine glycosylation pattern, short half life period and more hypersensitivity, and the like. Nimotuzumab is a humanized antibody obtained by humanized engineering of anti-EGFR murine derived monoclonal antibody. The light chain gene and heavy chain gene of the antibody are linked to different expression vector, respectively, for expression. Since there is a greater difference between the light chain expression and heavy chain expression, it tends to causes very low expression level of complete antibody molecule.